Category: 33468-69-8

Synthetic Route of 33468-69-8,Some common heterocyclic compound, 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, molecular formula is C4H3F3N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

4-(Trifluoromethyl)-1 /-/-imidazole (640 mg, 4.7 mmol) was stirred in dry THF (30 ml_) at room temperature under nitrogen. Lithium hexamethyldisilazide (1 M in THF, 4.2 ml_, 4.2 mmol) was added. After 45 minutes, a solution of Intermediate (1-13b) (1.42 g, 4.7 mmol) in dry THF (20 ml_) was added. The reaction was stirred for 12 hours. The reaction was quenched with saturated ammonium chloride and diluted with brine and ethyl acetate. Enough water was added to dissolve the precipitated salts. The aqueous layer was extracted with ethyl acetate, and the combined organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with 100% heptane gradient to 80% ethyl acetate/heptane. The appropriate fractions were combined, evaporated, and dried under high vacuum to afford (1-13c) as a yellow oil (689 mg, 2.39 mmol, 57%). m/z 289.2 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Trifluoromethyl)-1H-imidazole, its application will become more common.

Reference:
Patent; PFIZER INC.; BENBOW, John William; LOU, Jihong; PFEFFERKORN, Jeffrey Allen; TU, Meihua Mike; WO2010/29461; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, belongs to imidazoles-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 33468-69-8, category: imidazoles-derivatives

Sodium hydride (60 mass %) in 54 mineral oil (41.6 mg, 1.04 mmol) is added to a solution of 61 4-(trifluoromethyl)-1H-imidazole (96.3 mg, 0.694 mmol) in 56 DMF (5.0 mL) at 0 C. The mixture is stirred at room temperature for 30 minutes. 40 [3-[3-[6-(4-Isopropyl-1,2,4-triazol-3-yl)-2-pyridyl]-2-oxo-imidazolidin-1-yl]cyclobutyl] methanesulfonate (162.0 mg, 0.347 mmol) is added at room temperature, the mixture is heated to 90 C., and stirred for 17 hours. The reaction is quenched with water (20 mL) and the product is extracted with DCM (3×40 mL). The organic extracts are dried over Na2SO4 and concentrated in vacuo. The residue is purified by HPLC under the following conditions column: SunFire C18 5 mum, 30*100 mm, eluting with a gradient of 28%-43% of 57 ACN (0.1% FA) in 34 H2O (0.1% FA) over 10 minutes and stop at 17 minutes; flow rate: 30 mL/minutes. t(R) 7.5 minutes. The material is concentrated, dissolved in 21 water, and lyophilized to give the 62 title compound. ES/MS (m/z): 461.0 (M+1), 1H NMR (500 MHz, CDCl3) delta 8.36 (s, 1H), 8.33 (d, J=8.3 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.81 (t, J=8.0 Hz, 1H), 7.65 (s, 1H), 7.43 (s, 1H), 5.58-5.52 (m, 1H), 4.90-4.85 (m, 1H), 4.72-4.69 (m, 1H), 4.09 (t, J=8.0 Hz, 2H), 3.65 (t, J=8.0 Hz, 2H), 3.11-3.05 (m, 2H), 2.76-2.70 (m, 2H), 1.57 (d, J=7.0 Hz, 6H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(Trifluoromethyl)-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; Eli Lilly and Company; LIU, Lian Zhu; ZHANG, Haizhen; WANG, Xiaoqing; LIU, Gang; (14 pag.)US2019/71413; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 33468-69-8 as follows. Product Details of 33468-69-8

Preparation of 2-[3-ethylsulphanyl-5-(trifluoromethyl)-2-pyridyl]-3-methyl-6-[4-(trifluoromethyl)-imidazol-1-yl]imidazo[4,5-c]pyridine (I-74) Under argon, 99 mg (0.27 mmol) of 6-chloro-2-[3-ethylsulphanyl-5-(trifluoromethyl)-2-pyridyl]-3-methylimidazo[4,5-c]pyridine, 23 mul (0.15 mmol) of trans-N,N’-dimethylcyclohexane-1,2-diamine, 6.8 mg (36 mumol) of copper(I) iodide, 30 mg (0.22 mmol) of 4-(trifluoromethyl)-1H-imidazole and 64 mg (0.46 mmol) of potassium carbonate are added to 1 ml of degassed toluene. The vessel is closed and the reaction mixture is heated in a CEM Discover microwave reactor to 110 C. for 4 h. After cooling to room temperature, ethyl acetate is added and the mixture is filtered through a Celite bed, which is subsequently rinsed with ethyl acetate. The solvent is removed under reduced pressure and the residue is separated chromatographically by MPLC on silica gel (gradient: ethyl acetate/cyclohexane). In this way, 22 mg (100% purity, 18% yield) of 2-[3-ethylsulphanyl-5-(trifluoromethyl)-2-pyridyl]-3-methyl-6-[4-(trifluoromethyl)imidazol-1-yl]imidazo[4,5-c]pyridine are obtained. (log P (neutral): 3.36; MH+: 473; 1H NMR (600 MHz, CD3CN) delta ppm: 8.905 (3.0); 8.903 (3.0); 8.852 (1.6); 8.850 (1.6); 8.500 (1.9); 8.313 (1.5); 8.311 (2.1); 8.309 (1.4); 8.183 (1.7); 8.181 (1.7); 7.962 (3.4); 7.961 (3.4); 4.001 (16.0); 3.940 (0.4); 3.124 (1.1); 3.111 (3.4); 3.099 (3.5); 3.087 (1.2); 2.639 (0.7); 2.184 (55.7); 2.109 (1.2); 2.005 (2.2); 1.998 (195.7); 1.989 (2.7); 1.985 (1.8); 1.981 (10.0); 1.977 (18.2); 1.973 (26.5); 1.969 (18.0); 1.965 (9.0); 1.882 (1.2); 1.419 (0.4); 1.404 (0.7); 1.373 (0.6); 1.330 (4.1); 1.318 (9.0); 1.309 (1.6); 1.305 (5.2); 1.301 (3.4); 0.914 (0.6).

According to the analysis of related databases, 33468-69-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER CROPSCIENCE AKTIENGESELLSCHAFT; FISCHER, Ruediger; ALIG, Bernd; ILG, Kerstin; MALSAM, Olga; GOeRGENS, Ulrich; TURBERG, Andreas; LI, Jun; ZHERSH, Sergey; ARLT, Alexander; (58 pag.)US2017/73342; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H3F3N2

Synthesis of 3-methoxy-5-nitro-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridine To a stirred solution of 2-chloro-3-methoxy-5-nitropyridine (2 g, 10.60 mmol) in DMSO (30 mL) under an argon atmosphere were added potassium carbonate (6.70 g, 48.61 mmol) and 4-(trifluoromethyl)-1H-imidazole (1.7 g, 12.76 mmol) at room temperature. The reaction mixture was stirred at 50 C. for 16 h. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (20 mL). The obtained solid was filtered and dried in vacuo to afford 3-methoxy-5-nitro-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridine (1.4 g, 46%) as a yellow solid. 1H-NMR (DMSO-d6, 400 MHz): delta 8.97 (s, 1H), 8.65 (s, 1H), 8.45 (s, 1H), 8.44 (s, 1H), 4.11 (s, 3H); LCMS: 288.8 (M+1); (column; X-Select CSH C-18 (50*3.0 mm, 3.5 mum); RT 3.46 min. 0.05% aq TFA: ACN; 0.80 mL/min); TLC: 5% MeOH/CH2Cl2 (Rf: 0.4).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; FORUM Pharmaceuticals Inc.; Burnett, Duane A.; Bursavich, Matthew Gregory; McRiner, Andrew J.; (484 pag.)US2017/44182; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, molecular formula is C4H3F3N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Computed Properties of C4H3F3N2

To a solution of a tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (0.5 g, 1.8 mmol, CASRN: 15 8407-04-6) in dry DMF (4 mL) was added 4-(trifluoromethyl)-1H-imidazole (293 mg,2.16 mmol) and Cs2CO3 (1.17 g, 3.59 mmol). The reaction mixture was then stirred at 80 C for14 h. Insolubles were removed by filtration, and the filtrate was concentrated in vacuo. Thecrude residue was suspended in DCM and filtered through a pad of Celite to give a yellow oil,which was purified by flash chromatography with a 5i02 column, using an eluent mixture of nheptane and EtOAc (10% to 90%). This yielded the first fraction (301 mg) of the desired product as a colorless oil, and a second fraction (261 mg) of a mixture of the desired product with impurities. The second fraction was submitted for SFC purification, and the purified product was combined with the first fraction to yield 430 mg of the desired product as a colorless oil. MS(ESI): m/z = 334.2 [M+H].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 33468-69-8, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ANSELM, Lilli; BENZ, Joerg; GRETHER, Uwe; GROEBKE ZBINDEN, Katrin; HEER, Dominik; HORNSPERGER, Benoit; KROLL, Carsten; KUHN, Bernd; O`HARA, Fionn; RICHTER, Hans; (268 pag.)WO2020/35425; (2020); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 33468-69-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 33468-69-8 name is 4-(Trifluoromethyl)-1H-imidazole, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Step A: (+/-)-methyl 4-(3-methyl-1-(4-(4-(trifluoromethyl)-1H-imidazol-1-yl)phenyl)butoxy)benzoate Dimethylsulfoxide (1.5 mL) was added to a screw-top reaction vial charged with Intermediate (34) (128 mg, 0.339 mmol), 4-(trifluoromethyl)imidazole (55 mg, 0.406 mmol), copper (I) iodide (13 mg, 0.068 mmol), quinolin-8-ol (9.9 mg, 0.068 mmol), and potassium carbonate (92 mg, 0.67 mmol). The vial was evacuated and back-filled with nitrogen repeatedly then heated with stirring to 100 C. overnight. After 18 hours the reaction was diluted with saturated ammonium chloride (20 mL) and ethyl acetate (20 mL). The phases were separated and the organic layer was washed with water (2*20 mL) and brine (5 mL). The organics were dried over magnesium sulfate, filtered and concentrated. Purification by column chromatography (0-50% ethyl acetate in heptanes) gave (+/-)-methyl 4-(3-methyl-1-(4-(4-(trifluoromethyl)-1H-imidazol-1-yl)phenyl)butoxy)benzoate (65 mg, 44%) as a clear oil. 1H NMR (400 MHz, CDCl3, delta): 7.94-7.89 (m, 2H), 7.84 (s, 1H), 7.58 (s, 1H), 7.53-7.48 (m, 2H), 7.40-7.36 (m, 2H), 6.89-6.84 (m, 2H), 5.31 (dd, J=9, 4.6 Hz, 1H), 3.86 (s, 3H), 2.04 (m, 1H), 1.96-1.83 (m, 1H), 1.67-1.59 (m, 1H), 1.04 (d, J=6.6 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H). MS (M+1): 433.0.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(Trifluoromethyl)-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; PFIZER INC.; US2012/202834; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., Formula: C4H3F3N2

Production Example 58A mixture of 0.28 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole, 0.18 g of 4-(trifluoromethyl)-1H-imidazole, 0.55 g of potassium carbonate and 2 ml of DMF was stirred while heating at 50 C. for 1.5 hours. Then, the reaction mixture was cooled to room temperature. Water was added to the reaction mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.40 g of 2-{3-[4-(trifluoromethyl)imidazole-1-yl]pyridin-4-yl}-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as ?active compound 57?).Active Compound 571H-NMR (CDCl3) delta: 9.00 (d, J=5.2 Hz, 1H), 8.84 (s, 1H), 8.31 (d, J=5.1 Hz, 1H), 8.06-8.04 (m, 1H), 7.77-7.75 (m, 1H), 7.74-7.70 (m, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.52-7.50 (m, 1H)

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 33468-69-8.

Some common heterocyclic compound, 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, molecular formula is C4H3F3N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Computed Properties of C4H3F3N2

NMP (1.5 ml) was added to a mixture of 4-trifluoromethyl-1H-imidazole (65.8 mg, 0.484 mmol), methyl 3-iodo-6-methyl-2-pyridinecarboxylate D44 (67 mg), 4,7-bis(methyloxy)-1,10-phenanthroline (8.72 mg, 0.036 mmol), bis(copper(I) trifluoromethanesulfonate), benzene complex (6.09 mg, 0.012 mmol) and cesium carbonate (126 mg, 0.387 mmol) in a screw-topped vial with septum and the mixture was rapidly degassed via three vacuum/nitrogen cycles. The reaction mixture was then shaken and heated to 90 C. for 2 hours. The reaction mixture was heated to 110 C. for 2 hours. Another quantity of bis(copper(I) trifluoromethanesulfonate), benzene complex (6.09 mg, 0.012 mmol) was added and the mixture was heated with shaking to 110 C. for 2 hours. UPLC check shows all the methyl 3-iodo-6-methyl-2-pyridinecarboxylate has reacted but there are still only traces of the expected product methyl 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylate-closer scrutiny showed that signals in the mass spectrum corresponding to the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid co-elute with 4,7-bis(methyloxy)-1,10-phenanthroline in the UPLC. UPLC in basic conditions showed a better separation confirming the formation of the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid as well as de-iodinated product. The reaction mixture was cooled, diluted with water (15 ml) and loaded onto an ENV+ cartridge (1 g). The cartridge was eluted with water and then with MeOH. UPLC check of the water washes indicated they contain NMP as well as the deiodinated product and the excess 4-trifluoromethyl-1H-imidazole. UPLC check of the MeOH washes indicated they contained the acid 6-methyl-3-[4-(trifluoromethyl)-1H-imidazol-1-yl]-2-pyridinecarboxylic acid plus some impurities. The MeOH washes were combined and evaporated under reduced pressure to give a dark brown residue which was purified on the Biotage (mobile phase A was water made up with 0.1% formic acid, mobile phase B was acetonitrile made up with 0.1% formic acid. 12M C18 column was eluted with phase A for 2 column volumes then in gradient 0-50% A/B). The fractions containing the acid of the desired product were not pure by UPLC-they were combined and evaporated under reduced pressure to give 35 mg of a solid residue which was further purified by FractionLynx (Acid LC1, note a considerable quantity of the solid was insoluble in DMSO/MeOH). The fraction containing the desired product was evaporated under reduced pressure to give the title compound D121 (9 mg) of a pale orange glass. UPLC (Basic GEN_QC): rt=0.38 minutes, peak observed: 272 (M+1). C11H8F3N3O2 requires 271.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 33468-69-8, its application will become more common.

Electric Literature of 33468-69-8, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a mixture of 0.8 g of the intermediate compound 2-3, 0.36 g of 4-(trifluoromethyl)imidazole and toluene were added 0.74 g of potassium carbonate, 0.26 mL of trans-N, N?-dimethylcyclohexane-1,2-diamine and 0.15 g of copper iodide. The reaction mixtures were stirred at 120 C. for 24 hours, and cooled to room temperature, and thereto was added water, and the mixtures were extracted with ethyl acetate. The obtained organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to a silica gel column chromatography (hexane:ethyl acetate=3:2) to obtain the compound A-12 of the present invention 0.32 g. (1689) Compound A-12 of the present invention: 1H-NMR (CDCl3) delta: 1.37 (3H, t), 3.41-3.49 (2H, m), 6.49 (1H, d), 6.66 (1H, s), 7.54 (1H, d), 7.70-7.76 (2H, m), 8.04 (1H, s), 8.50 (1H, d), 8.90 (1H, d).

The synthetic route of 4-(Trifluoromethyl)-1H-imidazole has been constantly updated, and we look forward to future research findings.

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C4H3F3N2

Example 153 1,3,3-Trimethy1.6 [4..(trifluoromethyl)imidazol.. 1y1]indo1in2..one A suspension of 6-bromo-i,3,3-trimethylindolin-2-one (example la, 25.0 mg, 0.098 mmol), 4- (trifluoromethyl)-1H-imidazole (20.094 mg, 0.148 mmol) and potassium carbonate (40.8 mg,0.295mmo1) in acetonitrile (2.Oml) in a microwave tube was sparged with argon for 5 minutes. Then Cul (3.749 mg, 0.02 mmol) and N,N?-dimethylethane-i,2-diamine (0.0040 ml, 0.034 mmol) were added and degas sing was repeated. The tube was sealed and the reaction mixture was heated to 90C under microwave irradiation. The reaction mixture was concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 1 M aqueous HC1 solution. Theorganic layer was dried with sodium sulfate, filtered and the obtained solution concentrated in vacuo. The crude material was purified by silica gel chromatography using hexane/ ethyl acetate as eluent. The title compound was obtained as off-white solid (10 mg).MS ESI (m/z): 310.2 [(M+H)i

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 33468-69-8.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BRUNNER, Daniela; HILPERT, Hans; KOLCZEWSKI, Sabine; LIMBERG, Anja; MALBERG, Jessica; PRINSSEN, Eric; RIEMER, Claus; SHANKAR, Bavani G.; STOLL, Theodor; WO2014/202493; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem